Evaluating the Role of Re-Irradiation in the Management of DIPG: A Systematic Review and Meta-Analysis of Current Evidence

Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. Re-irradiation (re-RT) represents an emerging strategy aimed at improving outcomes for patients who experience recurrence or progression after initial radiation therapy (RT). While re-RT is increasingly used at progression, its survival benefit lacks robust quantification. This systematic review and meta-analysis aims to evaluate the impact of re-RT timing on OS and toxicity in pediatric DIPG.

This review was conducted in the PubMed/MEDLINE, Europe PMC, and Scopus (2014-2024), following PRISMA guidelines. Meta-analysis used random-effects models to pool OS after re-RT (primary outcome). Heterogeneity was quantified via I2 statistics. Secondary outcomes included symptom improvement and grade ≥3 toxicity.

Fourteen studies (n=357) were included. The pooled median OS after re-RT was 9.5 months (95%CI: 5.34-13.71), though substantial heterogeneity existed (I2=98.9%, p <0.001). Patients receiving re-RT had longer median OS from diagnosis than non-re-RT counterparts (20.8 vs. 8.3 months). Neurological symptom improvement occurred in 64-100% of patients, with triad symptoms (ataxia, cranial neuropathy, long-tract signs) showing greatest responsiveness. Only 1.4% (5/357 patients) experienced grade ≥3 complications (dysphagia, pontine necrosis, hemorrhage). The pooled hazard ratio (HR) or re-RT versus non-re-RT groups was 0.43 (95%CI: 0.28-0.67), indicating a 57% reduction in mortality risk.

This meta-analysis establishes that re-RT confers a statistically significant and clinically meaningful survival extension (median 9.5 months post re-RT), with low severe toxicity risk. While high heterogeneity reflects protocol variations (e.g., longer OS with >30 Gy regimens), re-RT consistently outperforms non-re-RT approaches. Re-RT also significantly reduces mortality risk (HR=0.43). We recommend standardized regimens using 1.8-2.0 Gy per fraction (≤24 Gy total) to optimize survival while minimizing toxicity. Future trials should prioritize dose optimization and patient stratification.